Abstract Severe obesity is the fastest growing category of pediatric obesity, with a reported prevalence near 6% in the United States. Unfortunately, conventional treatment approaches rarely result in sufficient weight loss in adolescents with severe obesity; therefore, innovative and effective strategies are desperately needed. The financial incentive model has been used successfully in adult obesity trials to address suboptimal adherence to lifestyle modification therapy and improves weight loss outcomes. Although yet to be investigated as a weight loss intervention among adolescents, financial incentives have been shown to improve many health-related behaviors in teenagers. Owing to the refractory nature of pediatric severe obesity, financial incentives are more likely to be effective if used in concert with a structured dietary plan such as meal replacement therapy (liquid shakes and frozen entres). In a recent trial, meal replacement therapy produced promising short-term weight loss in adolescents with severe obesity; however, initial weight lost by participants was regained after 4 months, owing to diminished adherence to the meal replacement regimen over time. Our concept is to capitalize on the synergy of meal replacement therapy and financial incentives to optimize weight loss and improve cardiometabolic risk factors and vascular health in teens with severe obesity. This study will afford a unique opportunity to address another key unanswered question related to the treatment of pediatric severe obesity: how much weight loss is necessary to elicit clinically-meaningful improvements in cardiometabolic risk factors and vascular health? Although evidence-based benchmarks have been established for adults, no such thresholds have been identified for youth with severe obesity. Therefore, we plan to conduct a 12-month randomized, controlled clinical trial to evaluate the effects of meal replacement therapy plus financial incentives on weight loss and cardiometabolic/vascular outcomes among 142 adolescents with severe obesity and to identify thresholds of weight loss required to achieve clinically-meaningful cardiometabolic/vascular improvements in this patient population. This research targets a significant public health problem, will utilize an innovative treatment concept and approach, and will generate new knowledge to guide selection of treatment type and intensification, ultimately exerting a powerful and sustained influence on the field of pediatric obesity.